Phospholipases catalyze the hydrolysis of fatty acid esters of acylphosphoglycerides. The substrates for the enzyme, phospholipids, are ubiquitous in biomembranes and are in intimate contact with membrane-bound enzymes and proteins. Phospholipases are involved in the maintenance of cellular function and viability through turnover and renewal of phospholipids. Furthermore, phospholipases have been implicated in diseases as atherosclerosis and in ageing processes. An interesting property of phospholipases is the marked enhancement of catalytic activity induced by a lipid-water interface such as presented by phospholipid micelles. The study of lipid-dependent enzymes is usually limited by the particulate nature of most systems. Phospholipase-A2 offers a unique opportunity to examine lipid-enzyme interactions of aggregated phospholipids with phospholipase tractable by magnetic resonance techniques. Magnetic resonance spectroscopy is capable of providing detailed information about intermolecular interactions which occur in enzyme-substrate complexes. This proposal concerns the application of magnetic resonance techniques to the study of the interactions of phospholipase with monomeric and aggregated phospholipids. A study of the structural requirements of phospholipase-A2 toward phospholipids will bear directly on problems concerned with the turnover of cellular membranes and ageing processes. Furthermore, the elucidation of phospholipase-phospholipid interactions has long range implications to the problems of membrane-bound enzymes. BIBLIOGRAPHIC REFERENCES: G. D. Markham and G. H. Reed, Synergistic Inhibition of Adenylosuccinate Synthetase by Nitrate and GDP, (1975) FEBS Lett. 54, 266-268. G. Michaels, Y. Milner, and G. H. Reed, Magnetic Resonance and Kinetic Studies of Pyruvate, Phosphate Dikinase. Interaction of Oxalate with Phosphorylated Form of the Enzyme. (1975) Biochemistry 14, 3213-3219.